Gamma-ketoaldehyde scavengers for alcoholic liver disease

DESCRIPTION (provided by applicant): Chronic alcohol overconsumption is the third largest risk factor for disease burden worldwide and is a frequent comorbidity of liver disease and cancer. While abstinence is a cornerstone of treatment, there is considerable interest in identifying other therapeutic interventions for alcoholic liver disease (ALD). Such advances are complicated by an incomplete understanding of the relationship between alcohol-specific metabolic responses and liver pathophysiology. The induction of a pro-inflammatory state, hallmark of ALD, appears to depend upon the unfavorable interplay among reactive oxygen species (ROS), protein adduct formation, and both the innate and adaptive immune responses. In this SBIR Phase I project, we hypothesize that the formation of highly reactive compounds, termed ?-ketoaldehydes (?-KA), formed primarily by non-enzymatic free radical catalyzed lipid peroxidation and secondarily by cyclooxygenases (COX) activity, is crucial for ethanol-induced liver injury.